Cancer arising from cervix is the number one cancer in women in many industrialized countries as well as emerging countries. About 30% of cancers in women are due to cervical cancer with more than 100,000 new cases diagnosed every year, e.g., in India. The estimated compounded annual growth rate (CAGR) for cervical cancer cases is 2.56% and at this growth rate approximately 175,000 new cases of cervical cancer will be detected in the year 2012.
One of the recommended tools for screening of cervical cancer is to detect cytological precursors of cancer in Papanicolaou tests (also called Pap-smear, Pap-test, cervical smear, or smear test), which is a screening test used in gynecology to detect premalignant and malignant processes in the cervical canal especially in the transformation zone.
In taking a Pap smear, a speculum is used to gather cells from the outer opening of the cervix of the uterus and the endocervix. The cells are examined under a microscope to look for abnormalities. The test aims to detect potentially pre-cancerous changes, which are, among others, caused by sexually transmitted human papilloma viruses. The test remains an effective, widely used method for early detection of pre-cancer and cervical cancer. The test may also detect infections and abnormalities in the endocervix and endometrium.
This procedure has been effective in bringing down the incidence of cervical cancer in the developed countries. However, Pap smear has a false negative rate of 10-29%. Reasons for the false-negative results are numerous and include sample collection errors (failure to obtain adequate cells on the slide in terms of cells representing the transformation zone), screening errors (failure to find abnormal cells on the slide), interpretation errors (failure to properly interpret abnormal cells), and miscellaneous laboratory errors related to staining problems, mislabeling, etc.
One of the major factors is that it is challenging for a pathologist to go through each of the cell in the slide. Each Pap smear slide has more than 10,000 cells of different morphological features. Depending on the stage of the cancer it is not unlikely that only a small fraction of cells (e.g., <<1%) in the sample is abnormal. This abnormality is detected by changes in the morphological features of the cell such as nuclear features, nuclear membrane, nuclear cytoplasmic ratio etc. Thus, careful observation of each cell feature is required to prevent false negative impression. This is a challenging task, considering the limited number of qualified pathologist in the field, the tremendous economical pressure under which they work, the limited time budget they have for each patient and the huge workload they are exposed to.